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Articles 1 - 20 of 20
Full-Text Articles in Molecular and Cellular Neuroscience
Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska
Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska
Student Theses and Dissertations
Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …
Expression Of Htyr In Drosophila As A Novel Model Of Parkinson’S Disease, Madeleine Callan
Expression Of Htyr In Drosophila As A Novel Model Of Parkinson’S Disease, Madeleine Callan
Scripps Senior Theses
Parkinson’s disease is a debilitating and often deadly neurodegenerative disease affecting a growing and large population. Its etiology has long remained elusive, and because no other organisms have Parkinsonian-like diseases, it is difficult to study PD using model organisms. Neuromelanin (NM), an insoluble melanin synthesized in the dopaminergic synthesis pathway in DA neurons, has recently been implicated in PD as a major causal factor. At high levels in DA lysosomes, it functions as a proteostatic pathway inhibitor–blocking dopaminergic neurons from breaking down harmful molecules until the lysosomes eventually degenerate as well as triggering autophagy, inflammation, and total neurodegeneration. Recently, neuromelanin …
Genetic Determinants Of Primary Nociceptor Sensitivity In Drosophila Melanogaster, Christine Hale
Genetic Determinants Of Primary Nociceptor Sensitivity In Drosophila Melanogaster, Christine Hale
Electronic Theses and Dissertations
Abnormal pain affects ~50 million adults nationwide. With many of the current treatment options for chronic pain, such as opioid analgesics, carrying side effects such as the threat for addiction, research into safer and more effective options for chronic pain relief is crucial. Abnormal alterations in nociceptive sensitivity, which is the sensitivity of peripheral sensory neurons that detect noxious stimuli, can underlie, and perpetuate chronic pain. However, much is still unknown about the mechanism of how these abnormal alterations in sensitivity occur. To help elucidate genetic components controlling nociceptive sensitivity, the Drosophila melanogaster larval nociception model has been used …
Genetic Circadian Mosaics And The Clock Network’S Contributions To Sleep, Lukasz Widziszewski
Genetic Circadian Mosaics And The Clock Network’S Contributions To Sleep, Lukasz Widziszewski
Dissertations, Theses, and Capstone Projects
Circadian rhythms are physiological and behavioral changes which follow a 24-hour cycle. Drosophila Melanogaster’s circadian clock neuronal network (CCNN) has been identified and several subpopulations have been characterized based on previous studies; the classifications of subpopulations of neurons within the CCNN are based on a return of anticipatory locomotor activity preceding the two daily light transitions (Lights on = dawn/Lights off = dusk). The neurons responsible for the return of anticipatory morning locomotor activity have been referred to as the M-cells, the group of neurons known to rescue evening anticipatory locomotor activity have been termed the E-cells. In this …
Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer
Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer
Publications and Research
Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. …
The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore
The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore
Graduate Theses, Dissertations, and Problem Reports
Neuromodulation is a nearly ubiquitous process that endows the nervous system with the capacity to alter neural function at every level (synaptic, circuit, network, etc.) without necessarily adding new neurons. Through the actions of neuromodulators, the existing neural circuitry can be adaptively tuned to achieve flexible network output and similarly dynamic behavioral output. However, despite their near ubiquity in all sensory modalities, the mechanisms underlying neuromodulation of sensory processing remain poorly understood. In this dissertation, I address three main questions regarding the mechanisms of one modulator (serotonin) within one sensory modality (olfaction). I begin by establishing a "functional atlas" of …
Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon
Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon
Electronic Thesis and Dissertation Repository
Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming neurons of …
The Wiring Logic Of Identified Serotonergic Neurons Across Olfactory Networks In Drosophila, Kaylynn E. Coates
The Wiring Logic Of Identified Serotonergic Neurons Across Olfactory Networks In Drosophila, Kaylynn E. Coates
Graduate Theses, Dissertations, and Problem Reports
Serotonin is a ubiquitous neuromodulator that confers flexibility in networks to modulate a wide array of behavioral and physiological processes. However, due to the complexity and heterogeneity of serotonergic systems, it has been challenging to determine the patterns of connectivity as well as the physiological contexts that influence individual serotonin neurons. In this dissertation, I use two serotonergic neurons which innervate the Drosophila olfactory system, the CSDns, as a model to explore these broad questions comprehensively using anatomical approaches. I first show that the CSDns have distinct connectivity relationships with populations of antennal lobe principal olfactory neurons and that their …
The Drosophila Neuroblasts: A Model System For Human Ribosomopathies, Sonu Shrestha Baral
The Drosophila Neuroblasts: A Model System For Human Ribosomopathies, Sonu Shrestha Baral
LSU Doctoral Dissertations
This dissertation describes the use of Drosophila neuroblasts (NBs) to model human ribosomopathies; the overall goal is to understand why specific stem cell and progenitor cell populations are the primary targets in nucleolar stress as seen in the ribosomopathies. Chapter 1 provides an overview of relevant literature. Chapter 2 describes nucleolar stress in Drosophila neuroblasts as a model for human ribosomopathies. For this, we induce nucleolar stress by using the UAS-GAL4 system to express RNAi that depletes Nopp140 transcripts, and we also employ homozygous, CRISPR-Cas9-generated Nopp140 gene disruptions with a systemic null phenotype (Nopp140-/-). Embryonic lethality was observed …
The Leucine-Rich Domain Of Rgnef: A Modifier Of Tdp-43 Toxicity In Drosophila Melanogaster., Benjamin Martin Withers
The Leucine-Rich Domain Of Rgnef: A Modifier Of Tdp-43 Toxicity In Drosophila Melanogaster., Benjamin Martin Withers
Electronic Thesis and Dissertation Repository
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive degeneration of motor neurons. Rho Guanine Nucleotide Exchange factor (RGNEF) like other RNA-binding proteins, has been observed to form inclusions in the spinal cord motor neurons of both sporadic and familial cases of ALS. RGNEF has been determined to be a pro-survival factor under stress conditions. When comparing expression of different constructs of RGNEF in HEK293T cells, a Leucine-rich domain containing fragment of RGNEF (L-Rich) was found to form aggregates under metabolic stress that co-aggregated with TDP-43, another ALS-linked RNA-binding protein.
In this thesis, I used both …
The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback
The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback
Theses and Dissertations--Biology
The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …
Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee
Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee
Theses and Dissertations
Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …
Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors., Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman
Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors., Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman
Biology: Faculty Scholarship
Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has …
Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner
Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner
Dissertations & Theses (Open Access)
Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …
Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang
Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang
Dissertations & Theses (Open Access)
Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …
Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, Juyeon Jo
Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, Juyeon Jo
Dissertations & Theses (Open Access)
Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive sensitization in both Drosophila and vertebrates. In Drosophila larval model of nociceptive sensitization, UV irradiation in results in epidermal apoptosis and thermal allodynia. TNF/Eiger is produced from dying epidermal cells and acts its receptor in nociceptive sensory neurons to induce thermal allodynia. Inhibition of TNF signaling results in attenuation of nociceptive sensitization whereas epidermal apoptosis still occurs in the absence of TNF. Major gaps in this model are the precise relationship between apoptotic cell death and production of TNF/Eiger, downstream signaling mediators for TNFR/Wengen, and target genes that alter nociceptive …
Reverse Genetic Screening Of Innexin Gap Junction Proteins In Drosophila Neurons, Shannon P. Fox
Reverse Genetic Screening Of Innexin Gap Junction Proteins In Drosophila Neurons, Shannon P. Fox
Senior Honors Projects, 2010-2019
The reflexive response and perception of pain (nociception) is an evolutionarily conserved process in animals. Pain can be a major health concern and current treatments often prove insufficient, especially in regards to chronic pain. Greater understanding of the molecular processes underlying pain sensation could lead to new and more effective treatments. The aim of this study is to investigate the molecular mechanisms of cold nociception in Drosophila melanogaster. A specific subset of peripheral sensory neurons (Class III dendritic arborization (da) neurons), are implicated in Drosophila larvae’s response to noxious cold.
Previous literature has associated a family of gap junction protein, …
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Open Access Dissertations
In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …
Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants, Kenny Nguyen, Hyun Sung, Peter J. Hollenbeck
Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants, Kenny Nguyen, Hyun Sung, Peter J. Hollenbeck
The Summer Undergraduate Research Fellowship (SURF) Symposium
The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, such as Parkinson’s disease. It has been proposed that proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. Though previously analyzed in the cell bodies and axons of neurons, the role of the PINK1/Parkin pathway in the synapse is unclear, and it is not known whether mitochondrial turnover occurs in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections …
Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock
Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock
Dissertations & Theses (Open Access)
Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.
To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …